title: Cilioplasm is a cellular compartment for calcium signaling in response to mechanical and chemical stimuli.
abstract: Primary cilia with a diameter of ~200 nm have been implicated in development and disease. Calcium signaling within a primary cilium has never been directly visualized and has therefore remained a speculation. Fluid-shear stress and dopamine receptor type-5 (DR5) agonist are among the few stimuli that require cilia for intracellular calcium signal transduction. However, it is not known if these stimuli initiate calcium signaling within the cilium or if the calcium signal originates in the cytoplasm. Using an integrated single-cell imaging technique, we demonstrate for the first time that calcium signaling triggered by fluid-shear stress initiates in the primary cilium and can be distinguished from the subsequent cytosolic calcium response through the ryanodine receptor. Importantly, this flow-induced calcium signaling depends on the ciliary polycystin-2 calcium channel. While DR5-specific agonist induces calcium signaling mainly in the cilioplasm via ciliary CaV1.2, thrombin specifically induces cytosolic calcium signaling through the IP3 receptor. Furthermore, a non-specific calcium ionophore triggers both ciliary and cytosolic calcium responses. We suggest that cilia not only act as sensory organelles but also function as calcium signaling compartments. Cilium-dependent signaling can spread to the cytoplasm or be contained within the cilioplasm. Our study thus provides the first model to understand signaling within the cilioplasm of a living cell.
authors.affiliation: Department of Medicine, College of Medicine, The University of Toledo, Toledo, OH, 43606, USA.
authors.forename: Xingjian
authors.initials: X
authors.lastname: Jin
authors.forename: Ashraf M
authors.initials: AM
authors.lastname: Mohieldin
authors.forename: Brian S
authors.initials: BS
authors.lastname: Muntean
authors.forename: Jill A
authors.initials: JA
authors.lastname: Green
authors.forename: Jagesh V
authors.initials: JV
authors.lastname: Shah
authors.forename: Kirk
authors.initials: K
authors.lastname: Mykytyn
authors.forename: Surya M
authors.initials: SM
authors.lastname: Nauli
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D061207:Calcium Ionophores / Q000494:pharmacology; D020013:Calcium Signaling; D002923:Cilia / Q000187:drug effects / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D057054:Molecular Imaging; D061251:Primary Cell Culture; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D012212:Rheology; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D059010:Single-Cell Analysis; D013314:Stress, Mechanical; D013552:Swine; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology
chemical_list: D020746:Calcium Channels, L-Type; D061207:Calcium Ionophores; D053496:Inositol 1,4,5-Trisphosphate Receptors; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D019837:Ryanodine Receptor Calcium Release Channel; D050396:TRPP Cation Channels; D013917:Thrombin; C419385:L-type calcium channel alpha(1C)